Groups of age-matched New Zealand white rabbits will be injected with the potent chromosome breaking chemical, streptonigrin (SN). At specific times post-treatment, we will evaluate oocytes in metaphase I and metaphase II of meiosis, and chromosomes of the fertilized ova for chemically induced cytogenetic lesions. Similarly treated does will be mated for the subsequent evaluation of inherited lesions in the post-implantation embryo and term fetus. These data will be compared with our earlier findings of SN-induced lesions in somatic cells and inherited lesions in six-day blastocysts from female rabbits. From the complete series of experiments we will determine the applicability of the somatic cell system as predictor of the risk of induction, transmission, and elimination of chemically induced lesions in the female germ cell. To estimate the risk to the second generation of exposure of the fetus to chemical clastogens, neonatal rabbits will be injected with SN during the period of oogenesis. When the rabbits have reached sexual maturity they will be mated and six-day blastocysts collected for evaluation of transmitted lesions. In a final experiment adult female rabbits will be treated with cyclophosphamide, methotrexate, methyl methanesulfonate, or cytosine arabinoside. The frequencies of induced lesions in marrow cells and lymphoblasts will be determined for comparison with the frequencies of inherited lesions in six-day blastocysts. From this study we hope to learn whether chemicals that damage DNA by alkylation, inhibition of folic acid synthesis, or base substitution also induce transmissible lesions in the dictyate oocyte, and whether somatic cell lesion frequencies are predictive of genetic risk in females exposed to these classes of chemicals.